Piperidine → HCID 178423315, compound

Participants

Reaction Steps

Using the method described in Example 30 by employing [1-(3,4-difluorophenyl)vinyl]pyrrolidine (freshly prepared before use from 3′,4′-difluoro acetophenone (Aldrich Chemical Company), pyrrolidine and TiCl4 (1.38 g, 6.60 mmol), 2-methyl-4,6-dichloro-5-nitropyrimidine (Example 76(b)) (1.40 g, 6.60 mmol), N,N-diisopropylethylamine (1.1 mL, 6.60 mmol), piperidine (1.0 mL, 10.6 mmol), NEt3 (1.1 mL) and SnCl2 (20 mL of a 2 M soln in DMF). The residue was purified by flash chromatography on silica gel with 95:5 HCl3/MeOH as eluant to give 395 mg (18%) of 6-(3,4-difluorophenyl)-2-methyl-4-piperidylpyrrolo[3,2-d]pyrimidine as a beige colored solid. This material (395 mg, 1.20 mmol) was dissolved in 10:1 EtOAc/MeOH (40 mL) and heated to boiling. To the hot solution was added 1 M ethereal HCl (1.20 mL, 1.20 mmol). The solution was left to cool to room temperature. The resulting solid was collected by filtration, washed with EtOAc (2×10 mL), Et2O (3×15 mL) and dried under vacuum at 60° C. to give 159 mg (6%) of the title compound as beige colored solid. Mp: 243-245° C. 1H NMR (DMSO-d6; 500 MHz): δ 1.71 (br s, 6), 2.57 (s, 3), 4.06 (t, 4, J=5.0), 6.85 (s, 1), 7.63 (q, 1, J=10.0), 7.89 (d, 1, J=8.1), 8.19 (dt, 1, J=1.3, 9.5), 12.01 (s, 1), 14.39 (s, 1). MS m/z: 329 (M+1 for free base). Anal. Calcd for C18H18F2N4.HCl.1.25H2O: C, 55.81; H, 5.60; N, 14.47; Cl, 9.15. Found: C, 55.95; H, 5.25; N, 14.62; Cl, 9.26.

Provenance & Evidence